Investigations from this laboratory have shown that the adrenergic sympathetic neuron is receptive to a specific nerve growth factor and is destroyed by antibodies to this factor. The latter effect became known as immunosympathectomy. Subsequently we have shown that the sympathetic nerve cells are extremely vulnerable to an analog of dopamine, 6- hydroxydopamine. Treatment of newborn animals with this drug results in the total and permanent destruction of sympathetic nerve cells (chemical sympathectomy). These findings prompted a series of investigations aimed at a careful evaluation of possible neurotoxic effects of drugs which interfere with the adrenergic transmission and biosynthesis, storage and release of the neurotransmitter. Results obtained in these last two years proved that specific lesions of sympathetic cells are in fact produced by prolonged and extensive treatment with bretylium tosylate and guanethidine. The effects of these drugs are not restricted to the peripheral sympathetic system but are apparent also in catecholamine containing neurons within the central nervous system. It is the object of this research project to analyze on a comparative basis the effects of several drugs interfering with the adrenergic function on growth, development and maintenance of peripheral and central CA neurons. The analysis of the possible neurotoxic effects will be carried out at the structural, ultrastructural, biochemical and pharmacological levels. The degree of functional impairment of the sympathetic nervous system found in different types of sympathectomy will be compared by monitoring the response of sympathectomized and normal animals to cold and other stresses. Furthermore, we plan to examine behavioral changes which may follow the alterations induced by these drugs in the adrenergic nervous system. Parallel to these studies, investigations will be performed on the serotoninergic system. A similar approach will be used as with the adrenergic neuron, by exploring the effect of serotonin analogs such as 5,6 dihydroxytryptamine on peripheral and central serotonin containing neurons.